Littrell et al provided such an educational program for 1 hour per week for 4 months to six men and six women taking olanzapine for schizophrenia or schizoaffective disorder.15 Patients in the behavioral group gained 0.5 kg, compared with a control group that gained 2.9 kg. Mean increase in BMI was less for the behavioral group (0.3 kg/m2) than for the control patients (0.9 kg/m2). Men in both groups gained more weight than did women.
Pharmacologic approaches
Antiobesity medications are generally reserved for patients with a BMI 30 kg/m2 (threshold for obesity) or for those with a BMI 27 kg/m2 (threshold for overweight is 25 kg/m2) who have additional risk factors for cardiovascular disease, stroke, or diabetes.16
For patients with schizophrenia, who typically have a BMI 27 kg/m2, the presence of these risk factors alone may be enough to warrant consideration of an antiobesity agent. Adding any new drug to a patient’s regimen, however, increases the risk of an adverse interaction.
Antiobesity drugs work by a variety of mechanisms, including decreasing appetite, decreasing fat absorption, and increasing energy expenditure. Drugs may reduce caloric intake by decreasing appetite (anorectic drugs) or increasing satiety (appetite suppressants). Centrally-acting sympathomimetics or serotonergic drugs may suppress appetite.
In studies up to 2 years, the appetite suppressant sibutramine, with mixed serotonergic and noradrenergic reuptake inhibition properties, has been shown to cause more weight loss than a placebo in populations without schizophrenia.17 According to one case report, sibutramine use was associated with new-onset psychosis.18
Common side effects of sibutramine include headache, dry mouth, anorexia, constipation, and insomnia. Regular monitoring of blood pressure is required. Do not prescribe this drug for patients with cardiovascular disease, and avoid co-prescribing with MAO inhibitors and serotonergics.
Orlistat reduces fat absorption from the GI tract.19 Common side effects are largely confined to the GI tract and include oily spotting, flatulence, fecal urgency, fatty/oily stool, and oily evacuation.
Combination therapies
Researchers are studying whether adding adjunctive agents to antipsychotics reduces weight gain.
Clozapine plus quetiapine A group of 65 patients who experienced a mean body weight increase of 6.5 kg while taking clozapine for 6 months were then given clozapine plus quetiapine at chlorpromazine-equivalent dosing during the next 10 months. The patients lost a mean of 4.2 kg, and their glycemic control improved. Elevated glycosylated hemoglobin (HbA1c) became normal in those subjects (20% of participants) who had developed type 2 diabetes while taking clozapine alone. The authors theorized that the weight loss diminished insulin resistance, leading to better control of serum glucose levels.20
Olanzapine plus amantadine A group of 12 outpatients with axis I or II diagnoses had responded well clinically to olanzapine but had gained an average 7.3 kg over 1 to 11 months. In an open-label study, they continued their dosages of olanzapine and also were given amantadine, 100 to 300 mg/d. Amantadine was chosen for this trial because of its possible release of dopamine.
No dietary changes were made, but subjects gained no additional weight after amantadine was added. Over the next 3 to 6 months, they lost a mean 3.5 kg, which was 50% of the weight gain associated with olanzapine administration.21
Clozapine plus topiramate In clinical trials, the anticonvulsant topiramate has been associated with significant weight loss for up to 12 months in patients with seizure disorders.22 This agent, which also has mood-stabilizing effects, may be useful both for mood stabilization and weight loss in tandem with antipsychotic therapy.
In a case study,23 a 29-year-old man with schizophrenia who failed several trials of antipsychotic drugs experienced significant improvement with clozapine, 800 mg/d. Over 2 years, however, he developed myoclonic jerks and gained 45.5 kg (a 49% increase over baseline). When topiramate was added, starting with 25 mg/d and increasing to 125 mg/d, his mood improved and the myoclonic jerks stopped. During 5 months of combination therapy, the patient lost 21 kg without changing his eating habits.
Olanzapine and nizatidine Agents that block histamine (H 2) receptors in the digestive tract may be associated with weight loss when given at high doses, although the mechanism by which they contribute to weight loss is unclear. In a double-blind, placebo-controlled study,24 the H 2 blocker nizatidine was given to patients with schizophrenia who were taking olanzapine, 5 to 20 mg/d. In a 16-week trial, 132 patients were randomized to receive adjunctive treatment with low-dose nizatidine (150 mg bid), high-dose nizatidine (300 mg bid), or a placebo.
After 16 weeks, nizatidine demonstrated a dose-response effect when combined with olanzapine. Average weight gain was: